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Immunological consequences of stress-related proteins – cytosolic tryparedoxin peroxidase and chaperonin TCP20 – identified in splenic amastigotes of Leishmania donovani as Th1 stimulatory, in experimental visceral leishmaniasis

Published online by Cambridge University Press:  11 December 2014

ANIL KUMAR JAISWAL ,
PRASHANT KHARE ,
SUMIT JOSHI ,
KEERTI RAWAT ,
NARENDRA YADAV ,
SHYAM SUNDAR  and
ANURADHA DUBE
ANIL KUMAR JAISWAL
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
PRASHANT KHARE
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
SUMIT JOSHI
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
KEERTI RAWAT
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
NARENDRA YADAV
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
SHYAM SUNDAR
Affiliation:
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
ANURADHA DUBE*
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
*
*Corresponding author. Division of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India. E-mail: anuradha_dube@hotmail.com, anuradha_dube@rediffmail.com
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Summary

In earlier studies, proteomic characterization of splenic amastigote fractions from clinical isolates of Leishmania donovani, exhibiting significant cellular responses in cured Leishmania subjects, led to the identification of cytosolic tryparedoxin peroxidase (LdcTryP) and chaperonin-TCP20 (LdTCP20) as Th1-stimulatory proteins. Both the proteins, particularly LdTCP20 for the first time, were successfully cloned, overexpressed, purified and were found to be localized in the cytosol of purified splenic amastigotes. When evaluated against lymphocytes of cured Leishmania-infected hamsters, the purified recombinant proteins (rLdcTryP and rLdTCP20) induced their proliferations as well as nitric oxide production. Similarly, these proteins also generated Th1-type cytokines (IFN-γ/IL-12) from stimulated PBMCs of cured/endemic Leishmania patients. Further, vaccination with rLdcTryP elicited noticeable delayed-type hypersensitivity response and offered considerably good prophylactic efficacy (~78% inhibition) against L. donovani challenge in hamsters, which was well supported by the increased mRNA expression of Th1 and Th2 cytokines. However, animals vaccinated with rLdTCP20 exhibited comparatively lesser prophylactic efficacy (~55%) with inferior immunological response. The results indicate the potentiality of rLdcTryP protein, between the two, as a suitable anti-leishmanial vaccine. Since, rLdTCP20 is also an important target, for optimization, further attempts towards determination of immunodominant regions for designing fusion peptides may be taken up.

Keywords

Leishmania donovanisplenic amastigotecytosolic tryparedoxin peroxidasechaperonin TCP20immunogenicitycured Leishmania patients/hamstersprophylactic efficacycellular immune response
Type
Research Article
Information
Parasitology , Volume 142 , Issue 5 , April 2015 , pp. 728 - 744
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Copyright
Copyright © Cambridge University Press 2014 

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